Polysaccharides from green sweet pepper increase the antineoplastic effect of methotrexate on mammary tumor cells

• Published in: International journal of biological macromolecules 2020-09, Vol.158, p.1071-1081
• Main Authors: Adami, Eliana Rezende, Corso, Claudia Rita, Turin-Oliveira, Natalia Mulinari, Galindo, Claudia Martins, Milani, Leticia, Stipp, Maria Carolina, da Silva, Liziane Cristine Malaquias, do Nascimento, Georgia Erdmann, Chaves, Pedro Felipe Pereira, Chequin, Andressa, Mariott, Marihá, da Silva, Luisa Mota, Klassen, Giseli, Ramos, Edneia A.S., Cordeiro, Lucimara M.C., Acco, Alexandra
• Format: Article
• Language: English
• Subjects: Breast tumor; Capsicum annuum; Interleukins
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2020.05.001

This study investigated the antineoplastic effects and toxicity of long-term treatment with polysaccharides from sweet green pepper (Capsicum annuum [CAP]), and concomitant treatment with CAP + methotrexate (MTX) on mammary tumor cells in vivo and in vitro. Ehrlich tumor cells were subcutaneously inoculated in female Swiss mice. The long-term treatment (31 days) with CAP (100 mg kg−1, p.o.) reduced the tumor growth and did not induce toxicity. The combined treatment protocol of 100 mg kg−1 CAP (p.o.) + 1 mg kg−1 MTX (i.p.) for 21 days inhibited the tumor growth in 95%, higher than the inhibition induced by MTX alone (1.0 or 2.5 mg kg−1, i.p.). In tumors, both CAP and CAP + MTX decreased the gene expression of Vegf, vessel area, and IL-4 and IL-10 levels, and increased IL-6 levels and the degree of necrosis. Treatment with CAP + MTX also increased TNF-α levels in tumors. Additionally, CAP + MTX treatment reduced the viability of human MDA-MB-231 and MDA-MB-436 mammary tumor cells in culture. In fact, CAP exerted antineoplastic effects in vivo and in vitro against mammary tumor cells, possibly by modulating inflammation and angiogenesis. CAP may be a promising adjunct chemotherapy with lower toxicity. •Long treatment with polysaccharides from sweet green pepper (CAP) has antineoplastic effect.•CAP and CAP + methotrexate (MTX) treatment modulate inflammation and angiogenesis in tumor microenvironment.•CAP increases the effects of MTX in mammary tumor cells from human and mice.